4-alkylidene-2-oxazolidones and process



4-ALKYLIDENE-2-OXAZOLIDONES AND PROCESS Margaret D. Cameron, Dayton,Ohio, assignor to Monsanto Chemical Company, St. Louis, Mo., acorporation of Delaware No Drawing. Application October 1, 1956 SerialNo. 612,975

17 Claims. (Cl. 260-307) This invention relates to azlactones and moreparticularly provides novel oxazolidinones and a new method of synthesisof such compounds.

By azlactones are herein meant cyclic compounds containing the ofalkynyl carbamates as illustrated by the following equation:

where each R represents hydrogen or a hydrogen radical and R representshydrogen, a hydrocarbon radical or a halohydrocarbon radical.

The present cyclization reaction whereby 4-alkylidene- 2-oxazolidinonesare prepared is highly surprising, since such cyclization of anacetylenic compound has not been known previously, nor have I have ableto cyclize a,,8- olefinic carbamates such as allyl carbanilate. It isparticularly unexpected that the resultant compound should bea'five-membered ring with an ex-ocyclic double bond, for cyclizations ofacetylenic compounds which have previously been reported have given ringcompounds wherein the acetylenic triple bond becomes an endocyclicdouble bond, the terminal acetylenic carbon atom being incorporatedint-o the ring system. It would, accordingly, be expected that thepresent reaction would give a sixmembered unsaturated ring system, but Ihave carried out a structure proof which disproves this expectation.

My structure proof is outined by the following set of equations:

l III 2,844,590 Patented July 22, 1958 ICQ H 0 OCNHCGHB oiiNHoaH,

W 02011 V o=o 0.1% VI (ll-Noam o-NHoQHE o=Noun o=o g 2 CH3 GE:

vn VH1 12:

' Thus, l-ethynylcyclohexanol (I) is hydrated to l-acetylcyclohexanol(II), a known compound. The carbanilate of I, having the structure IV,is identified as the acetylenic carbanilate by the infrared spectrum,showing the presence of an acetylenic triple bond. The carbanilate ofII, which is V, is free of acetylenic unsaturation and contains acarbonyl group. When each of IV and V is heated in the presence of abase, the identical compound, VI, is obtained. The formation of VI fromIV represents the novel synthesis of this invention as outlined above.The formation of VI from V must proceed by a route analogous to theprior art syntheses of oxazolinones from the carbamates of a-ketoalcohols:

In the present instance, in compound V the keto carbon atom is unable toform a double bond with the carbinol carbon atom, because three bonds ofthis cyclohexanol carbon atom are already fixed:

An imino double bond cannot be formed, for two bonds of the nitrogenatom are already fixed by attachment to carbon atoms, and in any case,the properties and characteristics of the product are not those of animino compound. Accordingly, the olefinic unsaturation in the cycliccompound obtained, the presence of which is evidenced by the spectra ofthe compounds, must be exocyclic. y

As proved by mixed melting points and comparison of infrared spectra,identical compound VI is obtained from compound IV and from compound V.The identity of compound VI as prepared by the two different synthesesis further proved by the conversion of samples thereof prepared via eachroute to the dinitrdphenylhydrazone of III, a known compound.

To the best of my knowledge, the 4-alkylidene-2-oxazohdmones provided bythis invention are novel compounds which have not been known hitherto.This class of compounds is of utility as intermediates in the synthesisof Z-oxazolidinones which contain an aliphaticallysaturated'substituents in the 4 position; the conversion of the presentcompounds to such oxazolidinones may be readily accomplished bycatalytic hydrogenation. The Z-oxazolidinones wherein an aliphaticallysaturated substituent 1s present onthe 4 position, are a known class ofcompounds having physiological, e. g., anticonvulsant activity, and alsouseful for such applications as plasticizers and solventsfornitrogen-containing polymers such as polyacrylonitrile.

Any of a wide variety of esters of acetylenic alcohols wlth carbamicacids may be employed in the present process for producing4-alkylidene-2-oxazolidinones. So far as I am presently aware, it isnecessary only that the ester be a,-acety1enically unsaturated and thata hydrogen atom should be attached to the nitrogen atom, from which itmigrates during ring closure to the ester acetylenic S-carbon atom. Theother substituents on the nitrogen atom and on the ester carbon atomsmay be hydrogen, or may be hydrocarbon radicals or hydrocarbon radicalssubstituted by negative substituents such as chlotine or bromine. In thepreferred embodiment of this invention, each R substituent on the estercarbon atoms, as identified in the above illustrated general equation ofthe reaction of the invention, is hydrogen or a hydrocarbon radicalcontaining up to 16 carbon atoms, and the 9 substituent R on thenitrogen atom of the molecule is hydrogen or is a hydrocarbon radicalcontaining up to 16 carbon atoms and substituted by from to halogenatoms having an atomic weight of from to 100, i. e., chlorine orbromine. Suchesters may readily be prepared by the reaction of theappropriate afi-acetylenically unsaturated alcohol with urea, wherebyesters of carbamic acid are obtained, or with acarbamyl chloride orisocyana'te, whereby there are obtained carbamate esters wherein thenitrogen atom of the molecule carries a single hydrogen atom as onesubstituent thereof.

One class of the presently useful esters are those wherein each R and R'in the formula of the presently useful starting materials is hydrogen oran aliphatic hydrocarbon radical. When R and each R is hydrogen, theabove formula represents 2-propynyl carbamate. Other presently usefulesters of carbamic acid, of the formula H NCOOCR CECR where each Rrepresents hydrogen or an alkyl radical, are e. g., esters of primaryacetylenic alcohols such as Z-butynyl carbamate, 2-pentynyl carbamate,Z-isopentynyl carbamate, Z-heptynyl carbamate,

4,4-dimethyl-2-pentynyl carbamate, 2-octynyl carbamate, 2-tridecynylcarbamate, Z-hexadecynyl carbamate, etc. Similarly, there may beutilizedthe carbamic acid esters of secondary acetylenic alcohols, suchas l-methyl-Z-pro- H pynyl carbamate, l-ethyl-Z-propynyl carbamate,l-isopropyl-Z-propynyl carbamate, l-ethynyloctyl carbamate, etc.; and oftertiary acetylenic alcohols such as 1,1-dimethyl-Z-propynyl carbamate,l,l-dipropyl-Z-propynyl carbamate, 1 methyl-l-ethyl 2 propynylcarbamate, 1 methyl-1-propyl-2-propynyl carbamate, 1ethynyl-lmethylpentyl carbamate, etc. I have further found that olefinicdouble bonds and acetylenic triple bonds which are notloc'ated alpha tothe carbinol carbon atom of the acetylenic alcohol used to form thepresently useful carbamatesare not susceptible to the presentcyclization reaction-attemperatures at which cyclization of thepresently useful esters occurs. 7

Accordingly, such unsaturation does not interfere in the presentsynthesis of cyclized compounds. Exemplary of u,B-acetylenicallyunsaturated esters containing additional aliphatic unsaturation anduseful in the process of the invention are alkenyl andalkynyl-substituted 0:,5-

'acetylenically unsaturated esters of carbamic acid, such as4-penten-2-ynyl carbamate, l-vinyl-2-propynyl car- 7-membered ring. Onesuch carbamate is l-ethynylcyclohexyl carbamate of the formula HzN C 0 0G 05011 which is presently an article of commerce. Otherl-alkynylcycloalkyl carbamates which may be cyclized in accordance withthe process of this invention include 1 ethynylcyclopentyl carbamate, 1ethynylcycloheptyl carbamate, l-ethynyl-4-methylcyclohexyl carbamate, 1-ethynyl-3,3,S-tfimethylcyclohexyl carbamate, l-ethynyl-2,2-dimethylcyclopentyl carbamate, l-ethynyl-4-isobutylcyclohexylcarbamate, l-(l-propynyDcyclohexyl carbamate, 1-(1-butyn-3-enyl)cyclohexyl carbamate, l-(lpropynyl)-3-methylcyclohexylcarbamate, etc.

A third class of presently useful carbamates are those wherein one ofthe substituents on the acetylenic ester radical is a cyclic radicalextrinsic to the carbinol carbon atom, i. e., a cycloalkyl or aromaticradical. Examples of such carbamates are 3-phenyl-2-propynyl earbamate,l-phenyl-Z-propynyl carbamate, 1-phenyl-2-butynyl carbamate,1-methyl-3-phenyl-2-propynyl carbamate, l-methyl-1-phenyl-2-propynylcarbamate, 4-cyclohexy1-2butynyl carbamate, l-cyclohexyl-2-butynylcarbamate, 3-cyclohexyl-l-methyl-Z-propynyl carbamate, etc.

In addition to the above-listed carbamates, the ,6- acetylenicallyunsaturated esters of carbamic acids wherein one substituent is presenton the carbamic acid nitrogen atom may also be cyclized by the processof this invention. The radical substituted on the carbamic acid nitrogenatom in the preferred embodiment of this invention is a hydrocarbonradical containing up to 16 carbon atoms and from 0 to 5 halogen atoms,having an atomic weight of from 30 to 100. One class of such esters ofcarbamic acids are the alkylcarbamate esters, which are readilyavailable by the reaction of an alkyl isocyanate with an acetylenicalcohol. Exemplary of the presently useful alkylcarbamate esters withaliphatic acyclic acetylenic alcohols are Z-propynyl methylcarbamate,2-propynyl ethylcarbamate, 2-propynyl n-propylcarbamate, 2-propynyln-butylcarbamate, 2-propynyl octylcarbamate, 2pr opynyl4,4-dimethyloctylcarbamate, Z-propynyl octadecylcarbamate,1-methyl-2-propynyl ethylcarbamate, 2-

butynyl butylcarbamate, 2-pentyn-4-enyl decylcarbamate,1-vinyl-2-propynyl ethylcarbamate, 1,1-dimethyl-2- decynylbutylcarbamate, etc. Alkynylcycloalkyl esters of alkylcarbamic acidswhich may be cyclized in accordance with the process of this inventioninclude, e. g., l-ethynylcyclohexyl butylcarbamate, l-ethyny-4-methylcyclohexyl octylcarbamate, ll-propynyl) -3 ,3 ,5-trimethylcyclohexyl dodecyclcarbamate, etc. Also available as startingmaterials for the process of this invention are the esters ofalkylcarbamic acids with other acetylenic alcohols containing cyclicsubstituents, such as l-phenyl-Z-propynyl carbamate, 3-phenyl-2-propynylcarbamate, 4-cyclopentyl- Z-butynyl ethylcarbamate, l-benzyl-Z-propynylbutylcarbamate, l methyl-3-cycloheXyl-2-propynyl dodecylcarbamate,l-p-tolyl-Z-propynyl butylcarbamate, l-phenyll-methyl-Z-butynylhexylcarbamate, 1,1-diphenyl-2-pentyn-4-enyl hexylcarbamate, etc. Alsocontemplated by this invention as starting materials for oxazolidinonesynthesis are the acetylenic esters of aliphatically substitutedcarbamates wherein the radical attached to the nitrogen atom containsaliphatic unsaturation, where these are available. Examples of suchesters are Z-propynyl 4-decenylcarbamate, l-methyl-l-phenyl-Z-propynyl9-decenylcarbamate, l-ethynylcyclohexyl 3-butynylcarbamate, etc.

A further embodiment of the process of this invention, which isparticularly preferred, comprises the cyclization of carbanilates andother aromatic carbamic acid esters of u,{3-acetylenically unsaturatedalcohols. The class of cyclizable carbanilates useful in the presentprocess is represented by the carbanilates of aliphatic alkynols such asthe carbanilates of primary acetylenic alcohols, e. g., Z-propynylcarbanilate, 2-pentynyl carbanilate, 2- tridecynyl carbanilate; ofsecondary alcohols, such as 1- methyl-2-propynyl carbanilate,l-propyl-Z-propynyl carbanilate, l-ethynyloctyl carbanilate; and oftertiary acetylenic alcohols, such as 1,1-dimethyl-2-propynylcarbanilate, l-methyl-1-propyl-2-propynyl carbanilate,l-ethynyll-methylpentyl carbanilate, l-butyl-l-methyl-2-pentyn-4- enylcarbanilate, etc. Equally susceptible to cyclization by the process ofthis invention are the l-alkynylcycloalkyl carbanilates as provided bymy copending application, Serial No. 612,978, of even date and commonassignment herewith, now abandoned. Examples of such l-alkynylcycloalkylcarbanilates are l-ethynylcyclohexyl carbanilate,1-(l-propynyl)cyclohexyl carbanilate, 1-(1- dodecynyl)cyclohexylcarbanilate, 1-ethynyl-4-methylcyclohexyl carbanilate,l-ethynyl-3,3,5-trimethylcyclohexyl carbanilate, 1 (1propynyl)-2,2-dimethylcyclo pentyl carbanilate, etc. Additionally, theremay be used in the present process carbanilate esters ofcyclo-substituted acetylenic alcohols such as l-phenyLZ-propynylcarbanilate, 3-phenyl-2-propynyl carbanilate, 4-cyclopentyl-2-butynylcarbanilate, l-p-tolyl-Z-propynyl carbanilate,l-rnethyl-l-phenyl-Z-propynyl carbanilate, 1,1- diphenyl-Z-propynylcarbanilate, 1-methyl-1-phenyl-2- butynyl carbanilate,1-phenyl-3-p-tolyl-2-propynyl carbanilate,l-phenyl-3-naphthyl-2-propynyl carbanilate, 3- biphenylyl-2-propynylcarbanilate, etc.

The present process is not limited to the carbanilates of acetylenicalcohols, and may equally be applied to acetylenic esters of otheraromatic acids. One such class of aromatic carbamates useful in thepresent process includes alkaryl carbamates such asar-methylcarbanilates [where 211- indicates ring substitution, asopposed to substitution on the N atom], e. g., 2-propynylp-methylcarbanilate, l-ethynylcyclohexyl 2,4-dimethylcarbanilate,lmethyl-l-phenyl-Z-propynyl p-isopropylcarbanilate, etc. Other classesof carbamates containing only one hydrocarbon substituent and availablefor cyclization by the present process include aralkylcarbamate esterssuch as 2- propynyl benzylcarbamate, 1,1-dimethyl-2-propynyldiphenylmethylcarbamate, l-(l-propynyl)cyclohexyl 2,2-diphenylpropylcarbamate, etc., and the acetylenic esters of polycyclicaromatic carbamates such as 2-propynyl naphthalenecarbamate, 2-propynylbiphenylcarbamate, 2- propynyl S-hexyl-l-naphthalenecarbamate, etc.

Also contemplated as starting materials for the present process are thecycloalkanecarbamic acid esters of acetylenic alcohols conforming to theabove formula, such as 2-propynyl cyclohexanecarbamate, 2-propynyl4-methylcyclohexanecarbamate, 1,1-diethyl-2-propynylcyclohexenecarbamate, etc.

In addition to the above-listed acetylenic esters with acids of theformula RNHCOOCRZCECR where each R represents hydrogen or a hydrocarbonradical, I have discovered that the present reaction is also applicableto esters wherein the radical represented by R contains negativesubstituents such as chlorine and bromine atoms and, in fact, thecychzation is particularly favored by the presence of negativesubstituents on the radical attached to the nitrogen atom of thecarbamate ester molecule. One class of negatively-substituted esters ofcarbamic acids susceptible to cyclization in accordance with thisinvention and especially preferred in the present process are thechlorocarbanilic and bromocarbanilic acid esters of n p-acetylenicalcohols. The acetylenic alcohol chlorocarbanilate and bromocarbanilateesters are a new class of compounds provided by my copendingapplication, Serial No. 612,921, of even date and common assignmentherewith, and are useful as biological toxicants. Such esters may bereadily prepared by the reaction of a halophenyl isocyanate with anacetylenic alcohol, preferably in the presence of a basic catalyst suchas pyridine.

Examples of the presently useful halocarbanilates are thehalocarbanilates of aliphatic acetylenic alcohols such as 2-propynyl2-chlorocarbanilate, 2-propynyl 3-chlorocarbanilate, 2-propynyl4-chlorocarbanilate, Z-propynyl 3,4-dichlorocarbanilate, 2-propynyl2,4-dichlorocarbanilate, 2-propynyl 2,4,5-trichlorocarbanilate,2-propynyl 3, S-dibromocarbanilate, 2-propynyl pentachlorocarbanilate,1,1-dimethyl-2-propynyl 3-chlorocarbanilate, 1-methyl-2- butynyl3-chlorocarbanilate, 1-(l-isobutenyD-l-methyl- 2-heptynyl3-chlorocarbanilate, etc. Another class of halocarbanilates useful inthe process of the invention are the esters of l-alkynylcycloalkylalcohols, especially those wherein the cycloalkyl radical contains a 5-to 7- membered alicyclic ring, said cycloalkyl radical containing atotal of from 5 to 10 carbon atoms. Exemplary of these esters arel-ethynylcyclohexyl S-chlorocarbanilate, l-ethynylcyclohexyl3,4-dichlorocarbanilate, l-ethynyl-4-methylcyclohexyl3-bromo-4-chlorocarbanilate, 1- (l-piopynyl)cyclohexyl 3-chlorocarbanilate, 1-( l-dodecynyl)cyclohexyl 4-ch1orocarbanilate,1-ethynyl-3,3,5-tri methylcyclohexyl 3-chlorocarbanilate, etc. Anotherclass of presently useful halocarbanilates are the esters ofarcmatically-substituted and cycloalkyl-substituted acetylenic alcohols,such as l-phenyl-Z-propynyl 3-chlorocarbanilate,l-phenyl-1-methyl-2-propynyl 3-chlorocarbanilate,l-phenyl-l-methyl-Z-propynyl 3,4-dichlorocarbanilate, lphenyl-Z-pentynyl3,4-dichlorocarbanilate, l-ethyl-3-phenyl-Z-propynyl 3,4dichlorocarbanilate, 4 cyclohexyl-lmethyl-Z-butynylpentachlorocarbanilate, etc.

Similarly, of utility as starting materials 'for cyclization to4-alkylidene-Z-oxazolidinones as provided by this invention are otherhalo-substituted carbamate esters of acetylenic alcohols such as2-propynyl 2-chloroethylcarbamate, 2-propynylS-chloro-l-naphthalenecarbamate, 2-propynyl3-chloro-4-methylcarbanilate, 2-propynyl 3- bromocarbanilate, 2-propynyl3,4-dibromocarbanilate, 1, l-dimethyl 2 propynyl 4-bromocarbanilate,l-ethynylcyclohexyl 5,8-dichloro-l-naphthalenecarbamate,l-methyl-l-phenyl-2-propynyl pentachlorocarbanilate, etc.

In accordance with the present invention, the esters of carbamic acidswith a,;8-acetylenic alcohols of the aboveillustrated formula arecyclized to form 4-alky1idene-2- oxazolidinones.

By the cyclization of esters of acetylenic alcohols with carbamic acid,there are provided 2-oxazolidinones wherein the nitrogen atom issubstituted only by hydrogen. Thus, e. g., by the cyclization of2-propynyl carbamate there is prepared 4-methylene-Z-oxazolidinone ofthe formula /O=0 HzC- -O Similarly, by the cyclization of esters ofcarbamic acid w th other primary aliphatic acetylenic alcoholsconta1n1ng no acetylenic hydrogen, there are prepared other4-alkyhdene-Z-oxazolidihones such as 4-ethylidene-2- oxazolidinone,4-propylidene-2-oxazolidinone, 4 hexylrdene-Z-oxazolidinone,4-nonylidene-2 oxazolidinone, .,4-

Y isohexadecylidene 2 oxazolidinone, 4 allylidene-Z-oxazoli'dinone,etc.- substituents on the carbinol'carbon atom of esters-of carbamicacid with aliphatic acetylenic alcohols produce S-substituted4-alkylidene-2-oxazolidinones, such as4-methylene-5-methyl-2-oxazolidinone, 4-methylene-S-ethyl-Z-oxazolidinone, 4 methylene 5,S-dimethyl-2oxazolidinone, 4-methylene-5-ethyl-5-methyl-2-oxazolidinone, 4 ethylidene-S-ethyl-S-heXyl-2-oxazolidinone,4-n1ethylene-S-butyl-Z-oxazolidinone, 4-methylene- 51-methyl-2-propynyl)-2-oxazolidinone, 5-decyl-2-oxazolidinone,4-ethylidene-5-propyl-Z-oxazolidinone,4-allylidene-5,S-dimethyl-Z-oxazolidinone, etc. Similarly, by thecyclization of aromatically substituted acetylenic carbamates inaccordance with this invention, there are provided4-alkylidene-2-oxazolidinones which may be substituted by aromaticradicals on the 4 and/or 5 position, such as4-benzylidene-2-oxazolidinone, 4-methylene-5-phenyl-2-oxazolidinone, 4benzylidene-S- phenyl-Z-oxazolidinone, 4-ethylidene-5-phenyl-2-oxazolidinone, 4-(2-phenylethylidene)-5,5-dimethyl-2-oxazolidinone,4-(4-biphenylylmethylidene) 2 oxazolidinone, 4- (p methylbenzylidene) 2oxazolidinone, 4-(2-a-naphthylethylidene)-5-propyl-2-oxazolidinone,4-benzylidene- 5 -t-butyl-5 -n1ethyl- 2oxazolidinone, 4-(2,4-dimethylhenzylid ene)-5,5-di-n-propyl-2-oxazolidinone, etc. Whenthe present cyclization process is applied to esters of carbamic acidwith cycloalkyl-substituted acetylenic alcohols wherein the carbon atomadjacent to the ester oxygen atom is extrinsic to the cycloalkyl ring,there are obtained, e. g., 4-(cyclohexylmethylidene)-5,5-di-methyl-2-oxazolidinone, 4 (2 cyclohexylethylidene)-2-oxazolidinone,4-(cyclohexylmethylidene) 5 methyl-2-oxazolidinone,4-methylene-5-cyclohexykl-oxazolidinone, etc.

Similarly, when the acetylenic esters of alkylcarbamic acids,arylcarbamic acids, and other esters of acids which can be derived fromthe corresponding isocyanates are cyclized, there are obtained3-substituted 4-alkylidene-2- oxazolidi'nones which may or may not carrysubstituents in the 5 position, depending on the substitution of theacetylenic alcohol portion of the ester. Thus, e. g., from 2 propynylmethylcarbamate is obtained 3-methyl-4- methylene-Z-oxazolidinone of theformula CHFGN CO HaC-O Similarly, by the cyolization of alkylcarbamateesters, there may be derived alkyl-subs'tituted 4-alkylidene-2-oxazolidinones such as 3 -ethyl-4-methylene-2-oxazolidinone, 3,5dimethyl 4-methylene-2-oxazolidinone, 3,5,5-trimethyl-4-methylene-2-oxazolidinone, 3 ethyl 4-ethylidene 5,5dimethyl-Z-oxazolidinone,3-ethyl-4-pentylidene-S,5-dimethyl-Z-oxazolidinone,3-butyl-4-hutylidene-5- ethyl S methyl-2-oxazolidinone,3-decyl-4-methylene-2- oxazolidinone, 3-(5,5dirnethylnonyl)-4-methylene-2-oxazolidinone, 3 butyl4-methylene-5-(2-methyl-3-pentynyl) S-methyl-Z-oxazolidinone, etc.Oxazolidinones derivable in accordance with the present invention fromthe esters of alkylcarbamic acids with acetylenic alcohols containingcyclic radicals are, e. g., 3-rnethyl-4-benzylidene-2-oxazolidinone,3-ethyi-4-benzylidene-Z-oxazolidinone,3-ethyl-4-methylene-5-phenyl-5-methyl-2-oxazolidinone, 3 butyl 4(cyclo'hexylmethyli'dene)-2-oxazolidinone, 3 butyl 4(Z-cyclohexylethylidene)-2-oxazolidinone,3-butyl-4-(cyclohexylmethylidene)-5,5-dimethyl-2- oxazolidinone, 3 hexyl4 (cyclopentylmethylidene)-2- oxazolidinone, 3-dodecyl 4-henzylidene-2oxazolidinone, 3 isopropyl 4 methylene 5 (2 phenylvinyl) 2oxazolidinone, 3 isopentyl 4-methylene-5,S-diphenyl-Z- oxazolidinone,3-butyl-4-ethylidene-5-phenyl-2-oxazolidinone,3-butyl-4-benzylidene-S-hexyl-S-methyl-2-oxazolidinone, 3 isodecyl 4-methylene-S-methyl-S-(2-(2,5,5-trimethyl-2-cyclohexenyl )ethyl)-2-oxazolidinone, etc.

4 methylene- By cyclization of a,j8-acetylenically unsaturated esters ofcarbamic acids wherein a cyclic radical is attached to the nitrogenatom, there are obtained 4 alkylidene 2 oxazolidinones bearing cyclicsubstituents on the 3 position. Examples of such oxazolidinone compoundsderived from cycloalkanecarbamates are derivatives of aliphatic acyclicprimary, secondary, and tertiary acetylenic alcohols, such as 3-cyclohexyl-4-methylene-2-oxazolidinone,3-cyclohexyl-4-ethylidene-2-oxazolidinone, 3-cyc1o'- hexyl 4dodecylidene 2-oxazolidi'none, 3-cyclohexyl-4-methylene-5,5-dimethyl-2-oxazolidinone, 3-cyclopropyl-4-methylene-Z-oxazolidinone,3-(4-isopropyl-l-methylcyclohexyl)-4-methylene-5,5-dimethyl 2oxazolidinone, 3-bicyclo[2.2.2]octyl 4 methylene 2 oxazolidinone, 3cyclohexenyl 4 propylidene 5,5 dimethyl 2 oxazolidinone, 3 (4 isopropyll-methylcyclohexyD-4- undecylidene-Z-oxazolidinone,3-cycIohexyl-4-methylene- 5-methyl-S-propyl-Z-oxazolidinone, 3bicyclo[2.2.l]heptenyl 4 (2 methylenepropylidene) 5 isopropyl2-oxazolidinone, etc.

Another embodiment of this invention comprises the oxazolidinonecompounds derived from the readily available esters of acetylenicalcohols with aromatic carbamic acids, providing 3-aryl oxazolidinonessuch as 3-phenyl- 4-methylene-2-oxazolidinone, 3 phenyl-4-methylene-5,5-dimethyl 2-oxazolidinone, 3-phenyl-4-ethylidene-5-ethyl- 2oxazolidinone, 3 phenyl 4 heptylidene-5-methyl-2- oxazolidinone, 3phenyl 4 pentylidene-S,S-di'methyl-Z- oxazolidinone, 3 phenyl 4propylidene S-isopropyl-S- methyl 2 oxazolidinone, 3phenyl-4-methylene-5,5-dipropyl-2-0Xazolidinone 3-ptolyl-4-methylene-2-oxazolidinone,3-o-tolyl-4-ethylidene-Z-oxazolidinone, 3-p-tolyl-4-methylene-5,5-dimethyl-2-oxazolidinone, 3-hiphenylyl-4-methylene-Z-oxazolidinone, 3 wnaphthyl-4-methylene-2- oxazolidinone, 3cuminyl 4-methylene-2-oxazolidinone,3-benzyl-4-rnethylene-2-oxazolidinone, etc. Among the4-alkylidene-Z-oxazolidinones provided by this invention and derivedfrom the esters of aromatic carbamic acids with acetylenic alcoholssubstituted by cyclic radicals are3-phenyl-4-benzylidene-Z-oxazolidinone, 3,5-diphenyl- 4-methylene 2oxazolidinone, 3-p-tolyl-4-(cyclopentylethylidene) 2-oxazolidinone,3,5-diphenyl-4-methylene- 5 methyl 2 oxazolidinone,3-phenyl-4-(Z-phenylethylidene) 2 oxazolidinone, 3 anaphthyl-4-methylene-5- phenyl 5 methyl 2-oxazolidinone,3-m-tolyl-4-benzylidene-S-methyl-Z-oxazolidinone, 3 biphenylyl 4(cyclohexylmethylidene)-5-methyl-2-oxazolidinone, etc.

In addition to the above oxazolidinones wherein hydrocarbon substituentsare present on the oxazolidinone nucleus, this invention provides theclass of 4 alkylidene- 2-oxazolidinoues carrying substituent radicals onthe nitrogen atom which bear negative substituents, i. e., bromine orchlorine atoms. Exemplary of the 3-haloalkyl-suhstituted oxazolidinonesprovided by this invention are3-(2-chloroethyl)-4-methylene-Z-oxazolidinone, 3- Z-bromoethyl-4-methylene-2-oxazolidinone, 3-trichloromethyl 4 isobutylidene 2oxazolidinone, 3 (2,2,2- trichloroethyl)-4-methylene-2-oxazolidinone,3-(2,2,3-trichloropropyl) 4 methylene 2 oxazolidinone, 3-chloromethyl 4ethylidene 5 methyl 5 phenyl 2- oxazolidinone, etc. Another andparticularly preferred embodiment of this invention comprises thehaloarylsubstituted oxazolidinones, e. g., 3(2-chlorophenyl)-4-methylene-2-oxazolidinone, 3- 3-chlorophenyl -4-methylene 2oxazolidinone, 3 (2,4 dichlorophenyl) 4- methylene-Z-oxazolidinone,3-(2,4,5-trichlorophenyl)-4- rnethylene 2 oxazolidinone, 3pentachlorophenyl- 4 methylene 2 oxazolidinone, 3 (4 chlorophenyl)- 4ethylidene 2 oxazolidinone, 3 (3 chlorophenyl)-4-methylene-5,5-dimethyl-2-oxazolidinone, 3-(3-brornophenyl) 4 methylene2 oxazolidinone, 3 (3 chlorophenyl) 4 ethylidene5-cyclohexyl-Z-oxazolidinone, 3 (3,5 dichlorophenyl) 4 (2cyclohexylethylidene)- 2 oxazolidinone, 3 (3 chlorobenzyl) 4 benzyli- 9dene 5 propyl 2 oxazolidinone, 3 (chlorophenyl)- 4 allylidene 5 phenyl 5methyl 2 oxazolidinone, 3 (5 chloronaphthyl) 4 methylene 2oxazolidinone, 3 (2 chloro 4 methylphenyl) 4 methylene- 2 oxazolidinone,3 (2 bromophenyl) 4 hexylidene- 5 phenethyl 5 methyl 2 oxazolidinone, 3(4'- chloro 4 biphenylyl) 4 undecylidene 2 oxazolidinone, 3(pentachlorobiphenylyl) 4 methylene 5- nonyl 5 methyl 2 oxazolidinone, 3(2 chloro- 4 isopropyl l methylcyclohexyl) 4 benzylidene-2-oxazolidinone, etc.

It will be noted that the above listing of the novel products of theinvention has not included the products of cyclization ofl-alkynylcycloalkyl esters of carbamic acids. When such esters arecyclized in accordance with this invention, the products of the reactionare spiro compounds, of the structure where R represents hydrogen, or ahydrocarbon radical of up to 16 carbon atoms, R represents hydrogen or ahydrocarbon radical of up to 16 carbon atoms substituted by to chlorineor bromine atoms, and R" Similarly, from l-alkynylcycloalkyl esters ofcarbamic acids of the presently preferred formula, may be prepared 4methylene 7,7,9 trimethyl 1 ox 3 azaspiro [4,5] decan-Z-one,3-methyl-4-methylene-1-ox-3-aza spiro[4,5]decan 2 one, 7,7 dimethyl 4methylene- 1 ox 3 azaspiro[4,4]nonan 2 one, 4 ethylidene- 1 ox -3azaspiro [4,61dodecan 2 one, 3 phenyl- 4 methylene l ox 3 azaspiro[4,5]decan 2 one, methylene 6,8,8 7 trimethyl 1 ox 3 azaspiro[4,5']-decan 2 one, 3 phenyl 4 methylene 7 methyl- 1 ox 3 azaspiro[4,5]decan 2one, 3 phenyl 4- methylene 6,8,8 trimethyl ox 3 azaspiro[4,5]- decan 2one, 3 phenyl 4 benzylidene 1 ox 3- azaspiro[4,5]decan 2 one, 3 (4chlorophenyl)- 4 decylidene 1 ox 3 azaspiro[4,4]nonane 2 one, 3 (3chlorophenyl) 4 allylidene 8 methyl 1- 0x 3 azaspiro [4,5]decan 2 one, 3(3,4 dichlorophenyl) 4 methylene 8 methyl l ox 3 azaspiro[4,5]decan 2one, 3 (3 bromophenyl) 4- (cyclohexylmethylidene) 7,7,9 trimethyl l ox3- azaspiro [4,5 decan-2-one, etc.

It will be appreciated by skilled stereochemists that the above listedcompounds are susceptible of existence in a variety of stericconfigurations, and that the present synthesis may produce mixtures ofenantiomorphs and diasterioisomers, depending on the substitution ofthestarting esters. All such stereoisomers are intended to be included bythe above listing of the compounds obtained in accordance with thisinvention, and by the appended claims.

In carrying out the process of the invention whereby them,fi-acetylenically unsaturated alcohol esters of carbamic acids arecyclized, these carbamic acid esters are it? simply heated at atemperature and for 'a time suflicient to elfect cyclization of thealcohol. The esters vary greatly in the ease with which cyclizationoccurs. Thus, e. g., in the process of synthesizing1,1-dimethyl-2-propynyl chlorocarbanilate by heating1,1-dimethylpropargyl alcohol with chlorophenyl isocyanate on a steambath for 2 hours in the presence of pyridine, followed by neutralizationof the pyridine with dilute hydrochloric acid and extraction of thereaction mixture with hot hexane, I have found that the product obtainedwas, not the expected ester,- but the cyclized product,3-(chlorophenyl)-4-methylene-5,S-dimethyl-Z-oxazolidinone. Thecarbanilates which are free of negative substituents are generally lessreactive and may require extended gentle heating for a period of 7-8hours or longer before undergoing cyclization. cyclized product has beendetected by infra-red analysis in an alkylcarbamate ester of propargylalcohol prepared from the isocyanate by a process comprising gentleheating in the presence of pyridine as described above, so

that even carbamates free of negative substituents may undergo thepresence cyclization process relatively readily, depending on the sterichindrance in the molecule and the freedom of the hydrogen atom attachedto the nitrogen atom to migrate to the p-acetylenic carbon atom.Excessive temperatures such as temperatures of 300 C. or above are to beavoided, since high heat can lead to undesired side reactions; andinstead, heating for more extended periods of time at lower temperaturessuch as the temperature of a steam bath is a preferred method ofeffecting the present cyclization.

I In many instances, the present reaction is accelerated by the presenceof basic catalysts. One preferred class of such catalysts includes thetertiary organic bases such as trimethylamine, N,N-dimethylaniline, orpyridine. In a preferred embodiment of the present reaction, the esterof a carbamic acid is prepared by the reaction of an acetylenic alcoholwith the carbamic acid generator, i. e., urea, a carbamyl chloride, oran isocyanate, in the presence of a base; the ester may then be cyclizeddirectly, if desired, by further heating, the base present as a catalystfor the esterification reaction functioning, as the heating iscontinued, to catalyze the cyclization. It will be appreciated thatother basic materials may also be used in the process of the invention:for example, inorganic catalysts such as basic metal oxides, e. g.,sodium hydroxide, potassium hydroxide, calcium oxide, etc., or analkoxide thereof, such as sodium ethoxide, or an alkali metal, can beused. Organic quaternary bases such as choline hydroxide may also beutilized as basic catalysts in'this process. In another embodiment ofthe present invention, the esters of carbamic acids useful in preparingoxazolidinones in accordance with this invention may be contacted with asolid basic catalyst, e. g., an ion exchange resin or a solid basicoxide such as alumina, to effect the cyclization. By the use ofcatalysts, the necessity for heating the esters to cause cyclization toproceed may be eliminated, and the cyclization may be caused to proceedat room temperature or below.

The presence of a solvent is not necessary, but solvents or .diluentsmay conveniently be employed as a reaction medium. Generally, theacetylenic esters of carbamic acids are more soluble in organic solventsthan the oxazolidinones, and the reaction medium may suitably be chosenso that the course of formation of the 4-alkyl idene-2oxazolidinones maybe followed by observation of the separation of the oxazolidinones fromthe solution of the carbamate. Advantageously, low-boiling solvents areemployed so that the reaction temperature may be controlled at thereflux temperature of the solution. Examples of suitable inert solventsare, e. g., hydrocarbons such as hexane or petroleum ether, benzene ortoluene; chlorinated compounds such as ethylene dichloride or carbontetrachloride; oxygenated solvents such as dioxane or ether; andnitrogen compounds such as di- On the other hand, the presence ofcal offrom 1 to 16 carbon atoms.

/ .g methylformamide, etc. Advantageously, under some circumstances, anexcess of an organic basic catalyst for the reaction, such as pyridine,may be utilized as the reaction medium.

Suband superatmospheric pressures may be applied to the ester or estersolution during the cyclization reaction if desired, but generally noadvantage is gained by pressure variation.

The time required for the reaction, as pointed out above, varies greatlywith the starting material and will also vary with the temperature towhich the acetylenic ester is exposed, and with the presence or absenceof catalyst. I have found that the occurrence of cyclization isgenerally accompanied by the formation of color in the reaction mixture,and this color change may conveniently be used as a gauge of theprogress of the reaction. However, the oxazolidinones of themselves areessentially colorless, and it is my belief that the color formation isdue to side reactions such as cleavage and aldol condensation. When thepresent reaction is carried out under conditions suppressing colorformation, the progress of the reaction may be followed by separation ofthe insoluble oxazolidinones from the solution of the carbamate, byspectral analysis of the reaction mixture, etc. The oxazolidinones aregenerally higher melting than the carbarnates, and may be alsoidentified, if desired, by melting point. The present products arereadily isolated by convenient means; in a preferred embodiment of thereaction, whereby acetylenic esters are refluxed in a lowboilingsolvent, the oxazolidinone may separate as a precipitate from which thesolution may be removed readily under reduced pressure, leaving theessentially pure product in a single step.

It will be appreciated that certain of the present 4alkylidene-Z-oxazolidinones, i. e., those doubly substituted on the 5position, may also be prepared via the alternative' route of mystructure proof as described hereinabove, by the cyclization of acarbamate ester of a l-acyl alcohol wherein the carbinol carbon atom isfree of hydrogen. These l-acyl alcohols may be prepared, inter alia, byhydration of an a,p-acetylenic alcohol by treatment with a strongmineral acid as illustrated by the following equation:

where each R is a hydrocarbon radical of from 1 to 16 carbon atoms, andR is hydrogen or a hydrocarbon radi- The formation of the carbamateester is then carried out byconventional means, i. e., by reaction withurea, a carbamyl chloride, or an isocyanate, after which the keto esteris cyclized by heating under dehydrating conditions, e. -g., in analcohol solution in the presence of a mineral acid or base. Thecyclization reaction proceeds as illustrated by the following equation:

where R and R are as defined hereinabove and R represents hydrogen or ahydrocarbon radical of from 1 to 16 carbon atoms substituted by from tochlorine or bromine atoms. So far as I am aware, such a synthesis hasnot been carried out prior to my present invention. Generally, exocyclicunsaturation is not readily obtained in chemical syntheses. While theprior art syntheses of oxazolin-S-ones, unsaturated compounds certain ofwhich are intermediates in the synthesis of penicillins, have givenexocyclic double bonds, this exocyclic unsaturation has always been ina-position to be stabilized by resonance with the keto carbon atom.Inthe present reaction, wherein there is formed an azlactone structure,the keto carbon atom being isolated between an oxygen and a nitrogenatom, no such resonance is possible; and

12 it is accordingly unexpected that it should be possible to carry outthis reaction successfully. However, inasmuch as such a synthesisrequires an additional step, hydration, as compared to my presentlyclaimed cyclization synthesis, and does not have the wide field ofapplicability of my synthesis consisting of a cyclization of acetylenicalcohol esters with carbamic acids, I prefer and claim'the lattersynthesis.

The presently provided 4-alkylidene-2-oxazolidinones when obtained inpure form are generally solid crystalline materials. They are useful fora variety of agricultural and industrial purposes. Thus, for example, aspointed out above, the present compounds are intermediates which can beconverted by hydrogenation, e. g., in the presence of Raneynickel, tothe corresponding 4-substituted 'Z-oxazolidinones wherein the4-substituent is saturated, these compounds being known to be usefulbiological toxicants, pharmaceuticals, solvents, etc. In addition, thepresent 4-alkylidene-2-oxazolidinones possess biological activity andare of utility as bactericides. Thus, for example, one of the compoundsof the invention is incorporated in a growth medium for bacteria such asnutrient agar, at a concentration of 1 part per thousand, to. inhibitthe growth of Micrococcus pyogenes var. aureus through out an incubationperiod of 5 days at 25 C. after the agar has been inoculated with thebacteria. Additionally, the compounds of the invention containing ahalo-substituted radical on the nitrogen atom thereof are of utility asagricultural fungicides. The present 4-alkylidene-2-oxazolidinones mayalso be used as herbicides, insecticides, hypnotics, etc.

The invention is illustrated but not limited by the following examples:

Example 1 This example illustrates the cyclization of an acetylenicester of an alkylcarbamate.

HCEGCHzOOONHCHaCHa GO Example 2 This example illustrates the cyclizationof a carbanilate of a primary acetylenic alcohol.

Propargyl carbanilate was prepared by mixing 25 g. of propargyl alcoholwith 49 g. of phenyl isocyanate in the presence of a few drops ofpyridine, the reaction mix ture beingstirred occasionally over a periodof 2 hours at room temperature. After decolorization andrecrystallization from hexane, the propargyl carbanilate obtainedmelted, in good agreement with the value reported in the literature, at62.462.7 C.

To 40 g. (0.23 'mole) of propargyl carbanilate prepared as describedabove were added ml. of pyridine,

'and'the mixture was refluxed for40 hours. After cooling,

13 the reaction mixture was drowned in water, and the resulting brownprecipitate extracted with hexane. By decolorization with charcoal andrepeated recrystallizations from hexane, benzene, and ethanol,3-phenyl-4-methylene- 2-oxazolidinone was isolated in 79% yield, aswhite crystals melting at 97.598 C.

Elemental analysis confirmed the expected composition of the product. Amixed melting point with the original carbanilate showed markeddepression of the melting point. The oxazolidinone was compared withpropargyl carbanilate by infrared analysis: the infrared spectrum of thepropargyl carbanilate shows bands for acetylenic ECH and for the NHgroup in the 3-micron region, and the carbonyl band appears in the6-micron region at 1700 cmf The infrared spectrum for the thermalcyclization product, 3-phenyl-4-methylene-2-oxazolidinone shows no handsin the 3-micron region, indicating the absence of acetylenic carbon andthe absence of amino hydrogen, and does contain a band corresponding tothe vinylidene group in the 14-micron region at 695 cm.- In addition,the carbonyl band in the 6-micron region is displaced to 1750 cm.-indicating a strained carbonyl group, i. e., a carbonyl group within acyclic ring rather than in a straight, freely rotating chain.

Example 3 This example illustrates the cyclization of a carbanilate of atertiary acetylenic alcohol.

CHrC-O 1,1-Dimethyl-2-propynyl carbanilate, m. 103-.2-103.5 C., wasprepared by adding 70.6 g. of 2-methyl-3-butyn- 2-ol to 100 g. of phenylisocyanate in 100 ml. of pyridine, and heating the resulting mixture ona steam bath for 2 hours. Without isolation of the carbanilate, thereaction mixture was then heated to 130 C. for 3 hours and let standovernight. The next day, 50 g. of crystals were filtered from the hotsolution and transferred to a Soxhlet extractor, where the crystals werecontinuously extracted with 250 m1. of hot hexane for 3 hours. Bycooling and filtration of the hexane extract, there were isolated 48.5g. of 3-phenyl-4-methylene-5,S-dimethyl-Z-oxazolidinone, m. 130.2l3l.5C., mixed M. P. with 1,1-dimethyl-2-propynyl carbanilate, 84.096.l C.The reaction mixture from which the 50 g. of crystals were separated waspoured into 750 ml. of water, precipitating additional crudeoxazolidinone product. A sample of the oxazolidinone decolorized withcharcoal and purified by repeated crystallizations from hexane andethanol was found to melt at l31.5l32 C. The identity of the product wasconfirmed by infrared spectral and elemental analysis.

Example 4 This example illustrates the cyclization of a carbanilate of al-alkynylcycloalkyl alcohol.

A solution of 68.5 g. of l-ethynylcyclohexanol in 100 ml. of pyridinewas added to 65.5 g. of phenyl isocyamate, and the reaction mixture washeated on a steam bath for 15 minutes, and then let stand at roomtemperature for 2 hours with occasional stirring. The cool reactionmixture was poured into a solution of 100 ml. of concentrated HCl in 800ml. of water; the solid which separated was filtered 0E andrecrystallized from hexane, giving l-ethynylcyclohexyl carbanilate aswhite needles, m. 97.097.4 C. Fifty, grams of this carbanilate weredissolved in 50 ml. of pyridine and refluxed 8 hours. The solidresulting from pouring the reaction mixture into 250 ml. of 20% HCl wasdecolorized with charcoal and recrystallized from hexane, whereby thereWas obtained 3 phenyl 4 methylene 1 ox 3 azaspiro [4,SJdecan-2-one, m.168.9-170 C.

Example 5 This example illustrates the cyclization of an ester of anacetylenic alcohol free of acetylenic hydrogen with a halo-substitutedcarbanilic acid.

Methylacetylene was introduced into a solution of lithium in liquidammonia, and to the resulting solution of lithium methylacetylide,diluted with ether, cyclohexanone was added, to prepare1-(l-propynyl)cyclo hexanol, m. 47 C., as described in my copendingapplication Serial No. 580,192, filed April 24, 1956. A mixture of g. of1-(1-propynyl)cyclohexanol with g. of 3-chlorophenyl isocyanate in 200ml. of pyridine was heated on a steam bath for 15 minutes, let stand for2 hours with occasional shaking, and poured into dilute hydrochloricacid, to precipitate out 1-(lpropynyl)cyclohexyl 3-chloroc-arbanilate,m. 995-1002 C. A solution of 50 g. of this chlorocarbanilate in 50 ml.of pyridine was refluxed for 8 hours and then poured into 250 ml. of 20%HCl, to give 45 g. of crude 3-(3- chlorophenyl) 4 ethylidene 1 ox 3azaspiro[4,5] decan-Z-one, as a sweet-smelling brown precipitate. Aportion of the crude product was decolorized with charcoal andrecrystallized from hexane to give a purified sample of the cyclizedproduct in the form of white crystals, m. l50.8-151.6 C. In the infraredspectrum of the product, the ECH and NH bands found in the spectrum ofthe chlorocarbanilate were absent, the olefinic band was present, andthe carbonyl group band was displaced as compared to thechlorocarbanilate spectrum, thus corroborating the postulated structure.

Example 6 Similarly, 50 g. of l-ethynylcyclohexyl 3-chlorooarbanilate,m. 119.9-120.2 C., prepared by reacting l-ethynylcyclohexanol with3-chlorophenyl isocyanate in pyridine at steam bath temperature for 15minutes, was dis solved in 50 ml. of pyridine and refluxed for 8 hours,after which the reaction mixture was poured into 250 ml. of 20% HOl toprecipitate 34 g. of crude product.

vBy treatment with decolorizing charcoal and repeated crystallizationsfrom hexane, 3 (3 chlorophenyl) 4- methylene l ox 3 azaspiro[4,5]decan 2one was isolated as yellow platelets, m. 143.6-143.8 C.

Example 7 By reaction of 168 parts of 2-methyl-3-butyn-2-ol with 338parts of 3-chlorophenyl isocyanate in the presence of 50 parts by weightof pyridine at steam bath temperature for 2 hours, followed by pouringthe reaction mixture into dilute hydrochloric acid and extracting theresulting precipitate with hexane, there was obtained1,1dimethyl-2-propynyl 3-chlorocarbanilate, m. 106.4- 107.0 C.

A flask charged with 250 ml. of hexane and 25 ml. of pyridine wasconnected to a Soxhlet extractor, in which was placed 140 g. of crude1,1-dimethyl-2-propynyl 3-chlorocarbanilate. After rapid extraction for4 hours, the hexane solution of the carbanilate was separated from theextraction apparatus, the hexane distilled 01?, and the remainingreaction mixture heated at 100 for 4 hours. The reddish-tan solidproduct was decolorized with charcoal and repeatedly recrystallized fromhexane and ethanol, whereupon 3-(3-chlorophenyl)-4-methylene-5,S-dimethyl-Z-oxazolidinone was obtained as white crystals, m.l02-102.5 C.

Example 8 rn. ll6.8117.2 C.

Twenty-five grams of 1,1-dimethyl-2-propynyl 3,441- chlorocarbanilateprepared as described above were dissolved in 50 ml. of pyridine andheated at about 100 C. for 8 hours. The reaction was poured into 300 ml.of 20% HCl, and the resultingprecipitate decolorized with charcoal andrepeatedly crystallized from ethanol and hexane. The purified3-(3,4-dichlorophenyl)-4- methylene-5,5 -dirnethyl-2-oxazolidinone soobtained melted at 140.2140.8 C.

Example 9 By procedures similar to those described above,l-ethyl-l-rnethyl-Z-propynyl 3,4-dichlorocarbanilate, m. 69.4- 69.6 C.,was prepared by reaction of 75 g. of 3,4-dichlorophenyl isocyanate with42 g. of 3-methyl-l-pentyn-3-ol in 100 ml. of pyridine at steam bathtemperature for 1 hour. Forty grams of the ester, obtained afterseparation from byproduct bis(dichlorophenyl) urea by recrystallizationfrom hexane, were dissolved in 50 ml. of pyridine, and the resultingsolution was refluxed for 8 hours. Treatment of the dark reactionmixture with'dilute hydrochloric acid, and decolorization andrecrystallization of the precipitate separating in the acidificationstep gave 3-(3,4-dichlorophenyl)-4-methylene-5-ethyl-5-methyl-Z-oxazolidinone as white needles, in. 88.6-88.8 C.

Example 10 When l-ethynylcyclohexanol was reacted with3,4-dichlorophenyl isocyanate in pyridine, the reaction mixture beingheated minutes on a steam bath and let stand 2 hours with intermittentshaking, the precipitate from neutralization of the reaction mixturewith hydrochloric acid was found to be partly cyclized. Thedichlorocarbanilate, separated by crystallization from hexane, m.119.7119.9 C.; the structure of this material was confirmed by infraredanalysis. The portion of the reaction product which had a wide (102-119C.) melting point range and which represented a mixture-ofdichlorocarbanilate and cyclized product was dissolved in pyridine, andthe solution refluxed for 8 hours. Treatment with aqueous hydrochloricacidproduced a brownish precipitate of crude 3-(3,4-dichlorophenyl)-4-methylene-l-ox-31 azaspiro [4,5] -decan-2-one.

"hours.

Example 11 This example illustrates the cyclization of an acetylenicalcohol ester with carbamic acid, wherein the substituents on thenitrogen atom are only hydrogen.

A mixture of 28 g. of propargyl alcohol and 30 g. of urea containingabout 1 g. of benzenesulfonic acid as catalyst was refluxed 12 hours;ammonia was evolved during the reaction. Heating was discontinued andthe reaction mixture extracted with boiling hexane; the hexane solutionwas evaporated to dryness on the water bath, and the resulting solidrecrystallized from water, to give 12 g. of 2-propynyl carbamate, in.43-44" C. The carbamate ester gradually cyclized on long standing atroom temperature, as evidenced by discoloration of the initiallywater-white crystals and confirmed by infrared analysis of thediscolored product.

Example 12 This example describes the evaluation of one of the presentcompounds containing a chloro-substituted nitrogen substituent as anagricultural fungicide.

Three two-week old tomato plants were immersed in a solution containingp. p. m. of3-(3,4-dichlorophenyl)-4-methylene-S-ethyl-S-methyl-2-oxazolidinone for48 The plants were then removed, the root systems washed and partiallytorn off, the plant roots immersed briefly in suspensions of the tomatowilt disease organism, Fusarium lycopersici, and the plants potted insterile soil. At the end of the growing period, when a control plantwhich had not received chemical treatment but had similarly been exposedto the wilt disease organism was dead, the plants were examined; and itwas found that the plants which had been treated with the oxazolidinonewere in vigorous health and had been completely protected from thedisease.

I Similarly, there may be employedas fungicides such compounds of theinvention as 3-(3,4-dichlorophenyl)-4- methylene-1-ox-3 -azaspiro [4,5]decan-Z-one, 3-(i-chlorophenyl)-4-methy1ene-5,5-dimethyl-2-oxazolidinone, etc.

While the invention has been described with reference to variousparticular preferred embodiments thereof, it will be appreciated thatnumerous modifications can be made without departing from the invention.

What is claimed is:

1. A 4-alkylidene-2-oxazolidinone of the formula where R represents asubstituent selected from the class consisting of hydrogen andhydrocarbon radicals of from 1 to 16 carbon atoms and R represents aradical selected from the class consisting of hydrogen and hydrocarbonradicals of from 1 to 16 carbon atoms substituted by from 0 to 5 halogenatoms, said halogen atoms having an atomic weight of from 30 to 100.

2. A 4-alkylidene-2-oxazolidinone of the formula where R represents ahydrocarbon radical containing from 1 to 16 carbon atoms and Rrepresents a hydrocarbon radical of from 1 to 16 carbon atoms containingfrom 1 to 5 halogen atoms, said halogen atoms having an atomic weight offrom 30 to 100.

3. A 4-alkylidene-2-oxazolidinone of the formula where R represents ahydrocarbon radical containing from 1 to 16 carbon atoms and from O to 5halogen atoms, said halogen atoms having an atomic weight of from 30 to100.

4. A 4-alkylidene-2-oxazolidinone of the formula where each R representsa hydrocarbon radical containing up to 16 carbon atoms and Ar representsa hydrocarbon radical containing up to 16 carbon atoms and containing atleast 1 benzene nucleus.

5. 4-methylene-Z-oxazolidinone.

6. 3-phenyl-4-methylene-5,5-dimethyl-Z-oxazolidinone.

7. 3-(3 chlorophenyl) 4 methylene-1-ox-3-azaspiro- [4,5ldecan-2-one.

8. 3-(3-chlorophenyl)-41-methylene-5,S-dimethyl-Z-ozazolidinone.

9. 3-(3,4-dichlorophenyl)-4-methylene-5,S-dimethyl-Z- oxazolidinone.

10. The process which comprises heating an ester of the formula i RCECCO C ONHR' where each R represents a substituent selected from the classconsisting of hydrogen and hydrocarbon radicals of from 1 to 16 carbonatoms, and R represents a radical selected from the class consisting ofhydrogen and hydrocarbon radicals of from 1 to 16 carbon atomscontaining from 0 to 5 halogen atoms, said halogen atoms having anatomic weight of from 30 to 100, for a time sufficient to effectcyclization of the said ester, and isolating from the resulting reactionproduct a 4-alkylidene-2-oxazolidinone of the formula RCH=ON R /CO R-?OR where R and R are as defined hereinabove.

11. The process which comprises contacting an ester of the formula RR020 A? O C ONHR where R and R are as defined hereinabove.

12. The process of claim 11 wherein the said ester is heated in thepresence of a basic catalyst for a time sufii- 1 cient to eifectcyclization of the said ester.

13. The process which comprises heating propargyl carbamate with a basiccatalyst for a time sufiicient to effect cyclization of the saidcarbamate and isolating from the resulting reaction product4-methylene-2-oxazolidinone.

14. The process which comprises heating 1,1-dimethyl- 2-propynylcarbanilate with a basic catalyst for a time sufiicient to effectcyclization of the said carbanilate, and isolating from the resultingreaction product 3-phenyl-4- methylene-5,S-dimethyl-Z-oxazolidinone.

15. The process which comprises heating l-ethynylcyclohexyl,3-chlorocarbanilate with a basic catalyst for a time sufiicient toeffect cyclization of the said chlorocarbanilate and isolating from theresulting reaction product 3-(3-chlorophenyl) -4-methylene-l-ox-3-azaspiro [4,5 decan-Z-one.

16. The process which comprises heating 1,1-dimethyl- 2-propynyl3-chlorocarbanilate with a basic catalyst for a time sufiicient toeffect cyclization of the said chlorocarbanilate and isolating from theresulting reaction product3-(3-chlorophenyl)-4-methylene-5,S-dimethyl-Z-oxazolidinone.

17. The process which comprises heating 1,1-dirnethyl- 2-propynyl3,4-dichlorocarbanilate with a basic catalyst for a time suflicient toelfect cyclization of the said dichlorocarbanilate and isolating fromthe resulting reaction product 3- 3,4-dichlorophenyl-4-methylene-5,S-dimethyl- 2-oxazo1idinone.

References Cited in the file of this patent UNITED STATES PATENTS2,399,118 Homeyer Apr. 23, 1946 UNITED STATES PATENT OFFICE CERTIFICATEOF CORRECTRN Patent Noo 2,844,590 July 22, 1958 Margaret D, Cameron A RIt is hereby certified that error appears in the pnntel specification ofthe above numbered patent requiring correction and that tie said LettersPatent should read as corrected below.

Column 1, line 43, for "have", second occurrence read=--== been column9, line 51, for "methylene-=6,8,8trimethyl" read W ;=ph y =4=propylidene line 54, after "trimethyl" insert l ;column 4, line 31, inthe formula, add to the lowest carbon atom of he substitut cyclohexylgroup w H column 17, line 24, for "Ar" red R line 31, for "-oza-=" readM -0Xaa Signed and sealed this 31st day of March 1959 (SEAL) Attest:

KARL H. AXLINE ROBERT C. WATSON Attesting Officer conmissioner ofPatents

1. A 4-ALKYLIDENE-2-OXAZOLIDIONE OF THE FORMULA